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摘要: 急性胰腺炎是一种常见的炎性胃肠道疾病,重症急性胰腺炎死亡率高且无有效的特异性治疗。近年来,高脂血症性急性胰腺炎的发病率不断上升且分型较重,但甘油三酯如何影响AP的发病及发展机制尚未完全阐明。最近研究发现甘油三酯的水解产物之一游离脂肪酸可以引起胰腺腺泡细胞中的多种细胞事件,影响急性胰腺炎的发生发展。本文将对游离脂肪酸的细胞病理作用及其对胰腺微循环的影响、甘油三酯水平与急性胰腺炎发病和严重程度的关系等方面进行综述,以期为高脂血症性急性胰腺炎治疗及预后判断提供新思路。Abstract: Acute pancreatitis is a common inflammatory gastrointestinal disease, and severe acute pancreatitis has a high mortality rate and no effective specific treatment. In recent years, the incidence of hyper triglyceridemic acute pancreatitis has been on the rise, and it has a variety of types. However, how triglyceride affects the pathogenesis and development mechanism of acute pancreatitis has not been fully clarified. Recent studies have shown that free fatty acids, one of the hydrolyzed products of triglyceride, may cause multiple cellular events in pancreatic acinar cells, which could affect the occurrence and development of acute pancreatitis. This paper will summarize different aspects such as Cytopathological effect of free fatty acids and its effect on pancreatic microcirculation, the relationship between triglyceride level and the incidence and severity of acute pancreatitis and so on, in order to provide new ideas for the treatment and prognosis of hyper triglyceridemic acute pancreatitis.
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Key words:
- acute pancreatitis /
- fatty acids /
- hypertriglyceridemia /
- pathogenesis
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[1] Petrov MS, Yadav D. Global epidemiology and holistic prevention of pancreatitis[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(3): 175-184. doi: 10.1038/s41575-018-0087-5
[2] Jin M, Bai X, Chen X, et al. A 16-year trend of etiology in acute pancreatitis: The increasing proportion of hypertriglyceridemia-associated acute pancreatitis and its adverse effect on prognosis[J]. J Clin Lipidol, 2019, 13(6): 947-953. doi: 10.1016/j.jacl.2019.09.005
[3] Boxhoorn L, Voermans RP, Bouwense SA, et al. Acute pancreatitis[J]. Lancet, 2020, 396(10252): 726-734. doi: 10.1016/S0140-6736(20)31310-6
[4] Noel P, Patel K, Durgampudi C, et al. Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections[J]. Gut, 2016, 65(1): 100-111. doi: 10.1136/gutjnl-2014-308043
[5] Lloret LC, Pelletier AL, Czernichow S, et al. Acute pancreatitis in a cohort of 129 patients referred for severe hypertriglyceridemia[J]. Pancreas, 2008, 37(1): 12-13.
[6] Tung YC, Hsiao FC, Lin CP, et al. High Triglyceride Variability Increases the Risk of First Attack of Acute Pancreatitis[J]. Am J Gastroenterol, 2023, 118(6): 1080-1090. doi: 10.14309/ajg.0000000000002198
[7] Hansen S, Madsen CM, Varbo A, et al. Low-Grade Inflammation in the Association between Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis: A Study of More Than 115000 Individuals from the General Population[J]. Clin Chem, 2019, 65(2): 321-332. doi: 10.1373/clinchem.2018.294926
[8] Goyal H, Smith B, Bayer C, et al. Differences in Severity and Outcomes Between Hypertriglyceridemia and Alcohol-Induced Pancreatitis[J]. N Am J Med Sci, 2016, 8(2): 82-87. doi: 10.4103/1947-2714.177307
[9] Li X, Ke L, Dong J, et al. Significantly different clinical features between hypertriglyceridemia and biliary acute pancreatitis: a retrospective study of 730 patients from a tertiary center[J]. BMC Gastroenterol, 2018, 18(1): 89. doi: 10.1186/s12876-018-0821-z
[10] Pascual I, Sanahuja A, García N, et al. Association of elevated serum triglyceride levels with a more severe course of acute pancreatitis: Cohort analysis of 1457 patients[J]. Pancreatology, 2019, 19(5): 623-629. doi: 10.1016/j.pan.2019.06.006
[11] Pothoulakis I, Paragomi P, Tuft M, et al. Association of Serum Triglyceride Levels with Severity in Acute Pancreatitis: Results from an International, Multicenter Cohort Study[J]. Digestion, 2021, 102(5): 809-813. doi: 10.1159/000512682
[12] Pothoulakis I, Paragomi P, Archibugi L, et al. Clinical features of hypertriglyceridemia-induced acute pancreatitis in an international, multicenter, prospective cohort(APPRENTICE consortium)[J]. Pancreatology, 2020, 20(3): 325-330. doi: 10.1016/j.pan.2020.02.010
[13] Scheele G, Adler G, Kern H. Exocytosis occurs at the lateral plasma membrane of the pancreatic acinar cell during supramaximal secretagogue stimulation[J]. Gastroenterology, 1987, 92(2): 345-353. doi: 10.1016/0016-5085(87)90127-2
[14] Pallagi P, Madácsy T, Varga Á, et al. Intracellular Ca2+ Signalling in the Pathogenesis of Acute Pancreatitis: Recent Advances and Translational Perspectives[J]. Int J Mol Sci, 2020, 21(11).
[15] Chang YT, Chang MC, Tung CC, et al. Distinctive roles of unsaturated and saturated fatty acids in hyperlipidemic pancreatitis[J]. World J Gastroenterol, 2015, 21(32): 9534-9543. doi: 10.3748/wjg.v21.i32.9534
[16] Kiss L, Für G, Pisipati S, et al. Mechanisms linking hypertriglyceridemia to acute pancreatitis[J]. Acta Physiol(Oxf), 2023, 237(3): e13916. doi: 10.1111/apha.13916
[17] Navina S, Acharya C, DeLany JP, et al. Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity[J]. Sci Transl Med, 2011, 3(107): 107ra110.
[18] Criddle DN, Murphy J, Fistetto G, et al. Fatty acid ethyl esters cause pancreatic calcium toxicity via inositol trisphosphate receptors and loss of ATP synthesis[J]. Gastroenterology, 2006, 130(3): 781-793. doi: 10.1053/j.gastro.2005.12.031
[19] Criddle DN, Raraty MG, Neoptolemos JP, et al. Ethanol toxicity in pancreatic acinar cells: mediation by nonoxidative fatty acid metabolites[J]. Proc Natl Acad Sci U S A, 2004, 101(29): 10738-10743. doi: 10.1073/pnas.0403431101
[20] Liu Q, Gu X, Liu X, et al. Long-chain fatty acids-The turning point between 'mild' and 'severe' acute pancreatitis[J]. Heliyon, 2024, 10(11): e31296. doi: 10.1016/j.heliyon.2024.e31296
[21] Habtezion A, Gukovskaya AS, Pandol SJ. Acute Pancreatitis: A Multifaceted Set of Organelle and Cellular Interactions[J]. Gastroenterology, 2019, 156(7): 1941-1950. doi: 10.1053/j.gastro.2018.11.082
[22] Danino H, Ben-Dror K, Birk R. Exocrine pancreas ER stress is differentially induced by different fatty acids[J]. Exp Cell Res, 2015, 339(2): 397-406. doi: 10.1016/j.yexcr.2015.09.022
[23] Jung S, Choi M, Choi K, et al. Inactivation of human DGAT2 by oxidative stress on cysteine residues[J]. PLoS One, 2017, 12(7): e181076.
[24] Wu J, Hu G, Lu Y, et al. Palmitic acid aggravates inflammation of pancreatic acinar cells by enhancing unfolded protein response induced CCAAT-enhancer-binding protein β-CCAAT-enhancer-binding protein α activation[J]. Int J Biochem Cell Biol, 2016, 79: 181-193. doi: 10.1016/j.biocel.2016.08.035
[25] Ben-Dror K, Birk R. Oleic acid ameliorates palmitic acid-induced ER stress and inflammation markers in naive and cerulein-treated exocrine pancreas cells[J]. Biosci Rep, 2019, 39(5).
[26] Mei Q, Zeng Y, Huang C, et al. Rapamycin Alleviates Hypertriglyceridemia-Related Acute Pancreatitis via Restoring Autophagy Flux and Inhibiting Endoplasmic Reticulum Stress[J]. Inflammation, 2020, 43(4): 1510-1523. doi: 10.1007/s10753-020-01228-7
[27] Iyer S, Bawa EP, Tarique M, et al. Know Thy Enemy-Understanding the Role of Inflammation in Severe Acute Pancreatitis[J]. Gastroenterology, 2020, 158(1): 46-48. doi: 10.1053/j.gastro.2019.11.039
[28] Zheng J, Wu J, Chen J, et al. Therapeutic effects of quercetin on early inflammation in hypertriglyceridemia-related acute pancreatitis and its mechanism[J]. Pancreatology, 2016, 16(2): 200-210. doi: 10.1016/j.pan.2016.01.005
[29] González-Moreno EI, González-González JA, Garza-González E, et al. Elevated Serum Triglycerides Associated With Systemic Inflammatory Response Syndrome and Persistent Organ Failure in Acute Pancreatitis[J]. Am J Gastroenterol, 2016, 111(1): 149.
[30] Rauen M, Hao D, Müller A, et al. Free Fatty Acid Species Differentially Modulate the Inflammatory Gene Response in Primary Human Skeletal Myoblasts[J]. Biology(Basel), 2021, 10(12): 1318.
[31] Baragetti A, Da DL, Moregola A, et al. Neutrophil aging exacerbates high fat diet induced metabolic alterations[J]. Metabolism, 2023, 144: 155576. doi: 10.1016/j.metabol.2023.155576
[32] Bae GS, Kim DG, Jo IJ, et al. Heme oxygenase-1 induced by desoxo-narchinol-A attenuated the severity of acute pancreatitis via blockade of neutrophil infiltration[J]. Int Immunopharmacol, 2019, 69: 225-234. doi: 10.1016/j.intimp.2019.01.051
[33] Qiu M, Zhou X, Zippi M, et al. Comprehensive review on the pathogenesis of hypertriglyceridaemia-associated acute pancreatitis[J]. Ann Med, 2023, 55(2): 2265939. doi: 10.1080/07853890.2023.2265939
[34] Sendler M, van den Brandt C, Glaubitz J, et al. NLRP3 Inflammasome Regulates Development of Systemic Inflammatory Response and Compensatory Anti-Inflammatory Response Syndromes in Mice With Acute Pancreatitis[J]. Gastroenterology, 2020, 158(1): 253-269. doi: 10.1053/j.gastro.2019.09.040
[35] Sarhan M, Land WG, Tonnus W, et al. Origin and Consequences of Necroinflammation[J]. Physiol Rev, 2018, 98(2): 727-780. doi: 10.1152/physrev.00041.2016
[36] 许威, 曾梦柳. 血液灌流联合血液滤过治疗高脂血症胰腺炎的研究进展[J]. 中国普通外科杂志, 2022, 31(3): 397-404.
[37] Tsai K, Wang SS, Chen TS, et al. Oxidative stress: an important phenomenon with pathogenetic significance in the progression of acute pancreatitis[J]. Gut, 1998, 42(6): 850-855. doi: 10.1136/gut.42.6.850
[38] Hong YP, Yu J, Su YR, et al. High-Fat Diet Aggravates Acute Pancreatitis via TLR4-Mediated Necroptosis and Inflammation in Rats[J]. Oxid Med Cell Longev, 2020, 2020: 8172714.
[39] Wu S, Pan L, Liao H, et al. High-fat diet increased NADPH-oxidase-related oxidative stress and aggravated LPS-induced intestine injury[J]. Life Sci, 2020, 253: 117539. doi: 10.1016/j.lfs.2020.117539
[40] Czakó L, Szabolcs A, Vajda A, et al. Hyperlipidemia induced by a cholesterol-rich diet aggravates necrotizing pancreatitis in rats[J]. Eur J Pharmacol, 2007, 572(1): 74-81. doi: 10.1016/j.ejphar.2007.05.064
[41] Zhang Y, Su SS, Zhao S, et al. RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome[J]. Nat Commun, 2017, 8: 14329. doi: 10.1038/ncomms14329
[42] Yang X, Zhao K, Deng W, et al. Apocynin Attenuates Acute Kidney Injury and Inflammation in Rats with Acute Hypertriglyceridemic Pancreatitis[J]. Dig Dis Sci, 2020, 65(6): 1735-1747. doi: 10.1007/s10620-019-05892-0
[43] Boulet MM, Cheillan D, Di Filippo M, et al. Large triglyceride-rich lipoproteins from fasting patients with type 2 diabetes activate platelets[J]. Diabetes Metab, 2020, 46(1): 54-60. doi: 10.1016/j.diabet.2019.03.002
[44] Sandoval J, Pereda J, Pérez S, et al. Epigenetic Regulation of Early-and Late-Response Genes in Acute Pancreatitis[J]. J Immunol, 2016, 197(10): 4137-4150. doi: 10.4049/jimmunol.1502378
[45] Rosenson RS, Shott S, Tangney CC. Hypertriglyceridemia is associated with an elevated blood viscosity Rosenson: triglycerides and blood viscosity[J]. Atherosclerosis, 2002, 161(2): 433-439. doi: 10.1016/S0021-9150(01)00656-6
[46] Wang L, Xu T, Wang R, et al. Hypertriglyceridemia Acute Pancreatitis: Animal Experiment Research[J]. Dig Dis Sci, 2022, 67(3): 761-772. doi: 10.1007/s10620-021-06928-0
[47] Ranade SS, Qiu Z, Woo SH, et al. Piezo1, a mechanically activated ion channel, is required for vascular development in mice[J]. Proc Natl Acad Sci U S A, 2014, 111(28): 10347-10352. doi: 10.1073/pnas.1409233111
[48] Nordstoga K, Sørby R, Olivecrona G, et al. Pancreatitis in hyperlipemic mink(Mustela vison)[J]. Vet Pathol, 2012, 49(3): 557-561. doi: 10.1177/0300985811417248
[49] 赵成思, 姚维杰, 王佐正, 等. 胰管支架治疗高三酰甘油血症性胰腺炎的疗效: 附33例报告[J]. 中国普通外科杂志, 2021, 30(9): 1023-1030.
[50] Maléth J, Balázs A, Pallagi P, et al. Alcohol disrupts levels and function of the cystic fibrosis transmembrane conductance regulator to promote development of pancreatitis[J]. Gastroenterology, 2015, 148(2): 427-439. doi: 10.1053/j.gastro.2014.11.002
[51] Cho SK, Kim JW, Huh JH, et al. Atherogenic Index of Plasma Is a Potential Biomarker for Severe Acute Pancreatitis: A Prospective Observational Study[J]. J Clin Med, 2020, 9(9): 2982. doi: 10.3390/jcm9092982
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